Effect of serum albumin on free fractions of phenobarbital and valproic acid in patients with convulsive seizures

The free fractions of phenobarbital and valproic acid were assayed with Free-Level system I (Syva) and by an enzymatic immunoassay technique (EMIT) in 186 patients under chronic anti-convulsant therapy at precisely 2 hrs after they had taken the medicine at breakfast. The free fractions of PB ranged from 49 to 53% in monopharmacy and from 50 to 55% in polypharmacy. Those of VPA ranged from 10 to 12% in monopharmacy and from 8 to 11% in polypharmacy. The regression lines of the free fractions in PB monopharmacy and PB polypharmacy against serum albumin concentration indicated a negative correlation. There was no difference between the free fractions in PB monopharmacy and polypharmacy at the same albumin concentration. The regression lines of the free fractions in VPA monopharmacy and polypharmacy against serum albumin concentration indicated a negative correlation. The free fractions of VPA did not vary under a total VPA concentration of 80 micrograms/ml, while those of VPA above a total VPA concentration of 90 micrograms/ml increased with the total concentration, in the monopharmacy groups. On the other hand, free fractions of VPA in the polypharmacy groups did not vary with the total VPA concentration.